Quality of life is impaired in MDS, but the role of hemoglobin level is unclear. To study the Hb–QoL correlation at diagnosis and 1 year later, patients filled out the EQ-5D questionnaire, assessing ...their mobility, self care, daily activities, pain/discomfort, and anxiety/depression, using scores of 0 (normal), 1 (mild/moderate), or 2 (poor). They also evaluated their health using a visual analogue scale, scoring from 0 (poor) to 100 (excellent). The anemia subgroups were: none/normal (Hb ≥ 12.5 g/dL), mild (10 ≤ Hb < 12.5), moderate (9 ≤ Hb < 10), severe (8 ≤ Hb < 9), or very severe (Hb < 8). LR-MDS patients (n = 127) and inpatient controls (n = 141) participated. The anemic patients had a poor QoL and the MDS patients had a lower QoL with a lower Hb. The controls had no QoL difference among the various anemia subgroups. In addition, the MDS QoL sharply decreased with an Hb of < 9. The MDS patients showed a wide QoL variability, i.e., different QoL scores in the same Hb subgroup, suggesting that other factors affect QoL (e.g., age and comorbidities). After 1 year (n = 61), the QoL was still poor for most MDS patients (including 27 patients with an increased Hb). In summary: (1) a poor QoL in MDS-anemia is non-linear, suggesting other influencing factors on QoL. (2) The sharp QoL drop with Hb < 9 g/dL challenges the transfusion Hb threshold. (3) The QoL in anemic MDS patients might differ from that in non-MDS patients. (4) Raising Hb, while recommended, does not guarantee an improved QoL.
OBJECTIVESThe use of antiplatelet agents is postulated to lead to improved outcomes in sepsis. We aimed to evaluate whether chronic, pre-hospitalization aspirin use leads to improved outcomes in ...patients with sepsis. METHODSWe conducted an observational cohort study among patients with sepsis, hospitalized in internal medicine wards in a single university-affiliated medical center. A propensity-score model was used to match and compare patients on chronic aspirin use to non-users. Patients with established cardiovascular disease were excluded. The primary outcome was survival rates at 30 days. Secondary outcomes included survival rates at 90 days, days of fever, length of hospital stay, and hospital readmission within 90 days. RESULTSA total of 1671 patients fulfilled the inclusion criteria. 533 chronic aspirin users were matched to 533 aspirin non-users. Survival rates were significantly higher among patients on chronic aspirin use (hazard ratio (HR) 0.67; 95% CI, 0.51-0.89)). This effect was highlighted in several subgroups of patients, as patients with chronic obstructive pulmonary disease (COPD) or those with chronic use of beta blockers showed the greatest survival benefit with aspirin use. Patients in the aspirin group also showed significantly higher 90 days survival rates (HR 0.69; 95% CI, 0.57-0.92; p = 0.006) and experienced less days of fever in comparison to the control group. DISCUSSIONPre-hospitalization treatment with aspirin for patients without established cardiovascular disease may be associated with mortality reduction, as shown in this is hypothesis-generating single center observational study.
Background
Tyrosine kinase inhibitors (TKIs) have significantly improved the life expectancy of individuals with chronic myeloid leukemia (CML), bringing it closer to that of the age-matched general ...population 1. However, clinical trial data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program indicates that only 3.8% of CML patients aged 75 or above participate in trials, despite this age group representing about 30% of CML patients 2. This study aims to assess the outcomes of elderly patients aged 75 years or older diagnosed with CML.
Methods
We conducted a retrospective study, using electronic medical records of consecutive CML patients aged ≥ 75 years, diagnosed between January 2002 and December 2021 at four hematological centers in Israel and Moffitt Cancer Center in Florida, United States (MCC). One-year and five-year overall survival (OS) rates were calculated for the whole cohort and for octogenarians (above 80 years). In addition, to assess if CML diagnosis affected life expectancy, we estimated the expected OS of the Israeli cohort based on life expectancy data from the central bureau of statistics (CBS). Kaplan-Meier curves were used to compare expected and observed median OS with the Log-rank analysis. Local Institutional Review Boards approved the study.
Results
A total of 123 patients (78 treated in MCC and 45 in Israel) aged ≥ 75 years were diagnosed with CML, with a median age of 79 (range: 75 - 100) years, and 55 patients (45%) were octogenarians. At the time of CML diagnosis 84% of had comorbidities, including cardiovascular risk factors in 90 patients (73%), while 50 patients (41%) had cardiovascular/cerebrovascular diseases. Most patients (93%) were diagnosed in chronic phase CML and high/intermediate EUTOS-LTS risk score (96%) treated with imatinib in the 1 st line treatment (69%). After a median duration of 15 (range:1-153) months on 1 st line treatment, 71 patients (58%) discontinued therapy primarily due to intolerance (n=51) while other causes included resistance (n=15), noncompliance/insurance issues (n=4) or progression to blast crisis (n=1). The 2 nd -line treatment included mainly 2 nd generation TKIs (n=53, 74%) (dasatinib-26, nilotinib -19 and bosutinib-8), while 9 patients received imatinib, 1 patient received nilotinib and imatinib, 5 patients received hydroxyurea and 3 patients were lost to follow-up. 35 patients (28%) reached 3 rd line of treatment (imatinib- 5, dasatinib- 3, bosutinib-12, nilotinib-5, ponatinib-2, asciminib-1, hydroxyurea -1, loss to follow up- 6) chiefly (28 patients) due to intolerance and others (7 patients) due to resistance.
The best response assessed by RQ-PCR showed deep molecular response (DMR) in 50%, major molecular response (MMR) in 16%, and complete cytogenetic response (CCyR) in 11% of patients with a median time to maximal response of 19 (range: 0.5-111) months. Nevertheless, treatment-free remission (TFR) was rare (n=1). During a median follow-up of 45 (0.4-198) months, 55 (45%) patients died, with cardiovascular complications (n=9), disease progression (n=8), infection (n=7), and secondary malignancy (n=4) being the main known causes.
The median OS for the whole cohort was 72.4 (53.1-91.7) months. Improved OS was documented in patients with an age adjusted charlson comorbidity index< 5 (vs. ≥5, p=0.007), those who achieved DMR (vs. no DMR, p=0.001) and median time to best response of 0-18 months (vs. ≥18, p=0.004). Moreover, OS was improved in patients who received 2 nd generation TKIs in 1 st line treatment, 91.1 (81.5-131) vs. 57.7 (35.4-79.9) months in those who received imatinib, (p=0.023). Older age did not affect OS; 1 and 5-year OS for the whole cohort was 86% and 29%, respectively, and 84.3% and 19.6% for the octogenarians, respectively (p=0.076).
In the Israeli cohort, while the median expected OS was 103.7 (24-164.7) months, the median observed OS was only 54.77 (2.1-195) months (p=0.03).
Conclusions
Elderly CML patients were often diagnosed in chronic phase with high/intermediate risk scores. The majority received imatinib as 1 st line treatment and achieved CCyR and MMR, with half of patients achieving also DMR. Surprisingly, patients treated with imatinib had worse OS compared to those receiving 2nd generation TKIs as 1st line treatment. Furthermore, the Israeli cohort analysis supports reduced life expectancy in the very elderly patients with CML.
Mantle cell lymphoma (MCL) is a difficult-to-treat B-cell malignancy characterized by cyclin-D1 (CD1) overexpression and deregulation of pathways such as B-cell receptor, PI3K/AKT/GSK3b, and NFkB. In ...the last decade, treatments such as BTK inhibitors and CAR T-cell therapy have demonstrated clinical benefits in MCL patients, but resistance inevitably develops and most patients eventually relapse. The evasion of apoptosis that is associated with MCL pathogenesis and therapy resistance frequently involves the upregulation of the pro-survival protein BCL-2. Correspondingly, several clinical trials have demonstrated the efficacy of the BCL-2 inhibitor venetoclax in producing high response rates in therapy-resistant MCL patients. Still, most MCL patients will eventually develop resistance to venetoclax. Currently, MCL treatments are pursued by studying novel agents with a broad spectrum of targets or by rationally combining therapies aiming for synergistic activities. Deferasirox (DFX) is a clinically approved iron chelator. We have shown previously that DFX exerts an anti-tumoral effect in MCL cells through ROS elevation, induction of DNA damage, modulating PI3K/AKT/GSK3b signaling, and enhancing CD1 degradation. The capacity of DFX to affect numerous targets establishes the basis for a possible synergistic interaction with other drugs, thus overcoming resistance in MCL.
To assess the potential of DFX to synergies with venetoclax and to overcome resistance to venetoclax in MCL.
The BCL-2 inhibitor, venetoclax, reduced the viability of Z138 and Jeko-1 cells (MCL celllines) in a dose-dependent manner. We found that clinically relevant concentrations of DFX synergized with venetoclax, prompting a reduction in the viability of these MCL cell lines with a combination index of <1. The synergy measured corresponds to a five-fold decrease in the IC50 concentrations of each drug separately. In agreement, the sensitivity of these MCL cells to DFX and venetoclax single- or cotreatments correlated with their ability to induce CD1 degradation. Finally, DFX was shown to induce apoptosis, reduce viability, and stimulate CD1 degradation in a venetoclax-resistant generated MCL cell line (Jeko-1R).
Our findings support the relevance of DFX-venetoclax combination treatment in MCL. A synergistic effect between these drugs provides potential, clinically feasible therapeutic options and a novel approach to overcome drug resistance in MCL.
Tyrosine kinase inhibitors (TKIs) have greatly improved chronic myeloid leukemia (CML) treatments, with survival rates close to the general population. Yet, for the very elderly, robust data remains ...limited. This study focused on assessing comorbidities, treatment approaches, responses, and survival for elderly CML patients. Our study was conducted on 123 elderly (≥ 75 years) CML patients across four centers in Israel and Moffitt Cancer Center, USA. The median age at diagnosis was 79.1 years, with 44.7% being octogenarians. Comorbidities were very common; cardiovascular risk factors (60%), cardiovascular diseases (42%), with a median age-adjusted Charlson Comorbidity Index (aaCCI) of 5. Imatinib was the leading first-line therapy (69%), while the use of second-generation TKIs increased post-2010. Most patients achieved a major molecular response (MMR, 66.7%), and half achieved a deep molecular response (DMR, 50.4%). Over half (52.8%) of patients moved to second-line, and nearly a quarter (23.5%) to third-line treatments, primarily due to intolerance. Overall survival (OS) was notably longer in patients with an aaCCI score below 5, and in patients who attained DMR. Contrary to expectations, the Israeli cohort showed a shorter actual life expectancy than projected, suggesting a larger impact of CML on elderly survival. In summary, imatinib remains the main initial treatment, but second-generation TKIs are on the rise among elderly CML patients. Outcomes in elderly CML patients depend on comorbidities, TKI type, response, and age, underscoring the need for personalized therapy and additional research on TKI effectiveness and safety.
Spontaneous resolution is common in patients with classic fever of unknown origin (FUO). Identifying predictors of spontaneous resolution could reduce the usage of unnecessary, invasive tests or ...empirical therapy, and furthermore reduce patient anxiety. Identify predictors associated with spontaneous resolution of FUO. A single center, retrospective, cohort study. All hospitalized patients who underwent an
18F
FDG PET-CT scan for the investigation of classical FUO between 1/2012 and 1/2020 were included. We compared patients with spontaneous resolution of fever and clinical symptoms, to those who were diagnosed with a specific etiology of FUO (subdivided to infectious diseases, non-infectious inflammatory diseases (NIID), and malignancies). Epidemiologic characteristics as well as laboratory and PETCT study results were compared. Variables that were found to be associated with spontaneous resolution of FUO on univariate analysis (
p
< 0.1) were entered into a multivariable regression analysis. The results are reported as odds ratios (OR) and 95% confidence intervals (CI). A total of 303 patients were hospitalized for the investigation of classical FUO and underwent complete assessment
.
Fever resolved without a diagnosis in 84/303 patients (28%). Variables that were associated with spontaneous resolution of FUO on multivariable analysis included: no anemia, no hypoalbuminemia and no pathological FDG uptake on PET-CT. In 17.8% (15/84) of studies, PET-CT yielded false-positive results that led to additional unnecessary, invasive investigation. Patients without anemia or hypoalbuminemia, and those without uptake on PET-CT are more likely to have spontaneous resolution of classical FUO.
In recent years the life expectancy in elderly patients with CML has approached that of the age-matched population and is similar to younger patients. In this study, we characterized and assessed the ...outcome of patients 75 years and older diagnosed with CML.
A multicenter, retrospective study of consecutive patients diagnosed in Israel and the Moffitt cancer center in Florida, United States (MCC) with CML at the age of ≥ 75 years. The 1- and 5-year overall survival (OS) were calculated. Event-free survival (EFS) was defined as death, progression, or a switch to 2nd line treatment due to intolerance or resistance to 1st line therapy. We estimated the median OS of the whole cohort at the time of CML diagnosis, hereafter termed expected OS, using the life expectancy according to the central bureau of statistics (CBS). The expected and the observed median OS were plotted using Kaplan-Meier curves and were compared using Log-rank analysis. The study was approved by the local Institutional Review Boards.
A total of 123 patients aged ≥ 75 years were diagnosed with CML between 2000 and 2022. The median age was 79 (range: 75 - 100) years. The median observed OS for the whole cohort was 48.5 (2.2-195) months compared to a median of 112 (27.6-150) months expected OS. OS and EFS were compared between patients receiving Imatinib vs. 2nd generation TKIs as 1st line treatment. OS was worse (71 months vs. not reached, P=0.021) for the group treated with imatinib in 1st line. EFS was similar between these groups (15 vs. 18 months, P=0.535).
According to the observed OS, life expectancy was shortened in elderly patients with CML. Noteworthy, compared to patients receiving 2nd generation TKI in 1st line treatment, patients receiving Imatinib had worse OS but similar EFS. An explanation of this result could be due to physician discretion due to comorbidities or insurance issues.
